Study of pro-inflammatory (TNF-?, IL-1?, IL-6) and T-cell-derived (IL-2, IL-4) cytokines in plasma and synovial fluid of patients with juvenile chronic arthritis: Correlations with clinical and laboratory parameters

Abstract

Acute phase proteins, synovial fluid (SF) cellular infiltrates, pro-inflammatory (TNF-alpha, IL-1alpha, IL-6) and Th1 (IL-2) and Th2 (IL-4) derived cytokine levels both in plasma and SF were examined in pauciarticular and polyarticular juvenile chronic arthritis (JCA) patients during the active (n = 22) and inactive (n = 14) period in order to determine pathogenic mechanisms and correlations between cytokines and laboratory parameters showing disease activity. The erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) and IgG concentrations were found to be significantly elevated in the active period of JCA. In pauciarticular JCA patients, when compared with their peripheral blood lymphocyte subpopulations, SF CD3+ cells (73.1%) and HLA-DR+ active T cells (22.5%) were found to be significantly increased. In the active period of JCA, plasma TNF-alpha and IL-6 concentrations were significantly elevated. Plasma IL-2 and IL-4 levels were not elevated and were found to be similar to those in the inactive phase and in healthy controls. SF IL-6, TNF-alpha and IL-1alpha levels were extremely high in all the patients. SF IL-4 and IL-2 levels were all undetectable. There was a significant correlation between ESR values and plasma IL-6 levels and between serum CRP levels and plasma IL-6 and TNF-alpha concentrations. In conclusion, increased local production of pro-inflammatory cytokines appears to account for the articular manifestations of JCA. The impaired production of anti-inflammatory Th2-derived cytokines (IL-4) seems to cause increased production of inflammatory cytokines acting on the balance between them. The deficit in IL-2 production was not suggested to be primarily involved in the pathogenesis. In addition, not only CRP and ESR values, but also plasma IL-6 and TNF-alpha concentrations may be used as markers of disease activity.

Anakinra in the treatment of polyarticular-course juvenile rheumatoid arthritis: safety and preliminary efficacy results of a randomized multicenter study

“…Increased production of the proinflammatory cytokine interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA) [9,10]. A number of publications also support the role of IL-1 in JRA of different onset types [11][12][13][14]. Consequently, the IL-1 receptor antagonist (IL-1ra) has been investigated as a therapeutic option to reduce the disease activity and joint damage caused by IL-1 [15].…”

New Treatment Strategies in the Treatment of Juvenile Idiopathic Arthritis

“…Elevated TNF-α levels have been identified in plasma and synovial fluid in patients with JIA [24] justifying that it is a major contributor to the inflammatory synovitis and joint damage in JIA. Tumor necrosis factor-α inhibitors are biological agents that block the immunological effects of this inflammatory mediator.…”

Secretion of pro‐inflammatory cytokines and chemokines and loss of regulatory signals by fibroblast‐like synoviocytes in juvenile idiopathic arthritis

“…Work has been done on the proteomic profile of synovial fluid from JIA 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, yet we do not have an understanding of the contribution attributable to the FLS in the disease. JIA FLS proved to be active, aggressive cells in the disease process, with profuse release of inflammatory cytokines, chemokines and loss of control over destructive mediators.…”